Therapeutic misadventures with acetaminophen: Hepatoxicity after multiple doses in children☆,☆☆,★,★★
Section snippets
Data Collection
Three cases derived from patients hospitalized at the Children's Hospital between 1979 and 1995 were identified by ICD9-CM chart search for fulminant hepatic failure and through direct involvement by members of the Division of Pediatric Gastroenterology and Nutrition. In each case the medical record was reviewed by one of the authors (JEH). MEDLINE and the International Pharmaceutical Abstracts database were searched during the summer of 1995 to identify published cases of acetaminophen-related
Results
Forty-seven patients fulfilled criteria for the diagnosis of acetaminophen hepatotoxicity associated with multiple dosing. Twenty-eight cases had previously been reported as case reports or in AAPCC abstracts.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 Thirteen cases were excluded because they were reports of single large ingestions, and 19 cases were excluded because there were insufficient data to conclusively determine that acetaminophen was the
Discussion
This report provides a compilation of all previously well-documented cases of repeated accidental overdosage of acetaminophen in children. It also includes 20 previously unreported cases and therefore represents the single largest collection of cases of liver injury associated with long-term acetaminophen administration in children. The 47 cases described in this report add to the eight nonoverlapping cases reported by Rivera-Penera et al.4 This total of 55 cases is small compared with the
Acknowledgements
We thank Andrea Smith, Patricia Calvin, and Catherine McGraw for assistance in the preparation of the manuscript, table, and figures. We also thank Drs. William F. Balistreri and John C. Bucuvalas for their helpful suggestions regarding the content of the manuscript. Ms. Barbacci's contribution to this report was originally done in connection with gathering literature for litigation involving acetaminophen-related injuries to children. Dr. Heubi has served as an expert witness in
References (44)
- et al.
Hepatic damage and death from overdose of paracetamol
Lancet
(1973) - et al.
Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure
Hepatol
(1995) - et al.
Fatal acetaminophen overdosage in a young child
J Pediatr
(1978) The laboratory in the diagnosis and management of acetaminophen and salicylate intoxications
Pediatr Clin North Am
(1980)- et al.
1988 Annual Report of the American Association of Poison Control Centers National Data Collection System
Am J Emerg Med
(1989) - et al.
1987 Annual Report of the American Association of Poison Control Centers National Data Collection System
Am J Emerg Med
(1988) - et al.
Increased acetaminophen-induced hepatotoxicity after chronic ethanol consumption in mice
Toxicology
(1983) - et al.
Effect of fasting on metabolite-medicated hepatotoxicity in the rat
Gastroenterology
(1979) - et al.
Mechanisms of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat
Biochem Pharmacol
(1987) - et al.
Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes
Biochem Pharmacol
(1993)
Fulminant hepatitis associated with centrilobular hepatic necrosis in young children
J Pediatr
Acute paracetamol poisoning
Br Med J
Acetaminophen overdose
Am J Med
Outcome of acetaminophen overdose in pediatric patients and factors contributing to liver toxicity
J Pediatr
Association of acetaminophen hepatotoxicity with fasting and ethanol use
JAMA
Acetaminophen poisoning
J Fam Pract
Liver failure in an infant
Can Med Assoc J
Probable acetaminophen toxicity in an 18-month-old infant due to repeated overdosing
Clin Pediatr
Fatal paracetamol poisoning from benorylate therapy in child with cystic fibrosis
Lancet
Fatal acetaminophen toxicity in a 2-year-old
J Indiana State Med Assoc
Acetaminophen poisoning in infancy
Am J Dis Child
Acute liver failure and encephalopathy in a 15-month old infant
Am J Dis Child
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2022, Toxicology ReportsCitation Excerpt :Accordingly, the perception of paracetamol as a safe OTC drug has become very misleading as this has led to a high rate of paracetamol toxicity. Liver failure has been reported even with doses just more than the maximum therapeutic dose [11,16–18]. According to the United States Food and Drug Administration (FDA) guidelines, it is safe to consume up to a maximum daily dose of 4000 mg of acetaminophen [19–21].
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2021, Cummings Pediatric OtolaryngologyFatal acetaminophen poisoning with hepatic microvesicular steatosis in a child after repeated administration of therapeutic doses
2020, Forensic Science InternationalCitation Excerpt :Acetaminophen was administered at a dose of 16.7 mg/kg every four hours for twelve hours, giving a cumulative dose of 66.6 mg/kg in twelve hours, which is lower than the dose of 75 mg/kg per day considered safe in children aged below six years, and much lower than the commonly accepted toxicity threshold of 150 mg/kg per day. Unintentional administration of supratherapeutic doses of acetaminophen is known to induce hepatotoxicity and to be associated with high mortality [13–16]. It is also known that caregivers can be reluctant to accept the fact that they made a mistake contributing to child’s illness.
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From the Division of Pediatric Gastroenterology and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio; the Department of Medicine, George Washington University, Washington, D.C.; and Armed Forces Institute of Pathology, Washington, D.C.
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Supported in part by U.S. Public Health Service grant no. M01 RR-08084 from the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.
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Reprint requests: James E. Heubi, MD, Clinical Research Center, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039.
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